The roles of JAK2/STAT3 signaling in fusion of the secondary palate.
Cleft palate
Folic acid
JAK2/STAT3
Palatal fusion
p63
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
01 10 2023
01 10 2023
Historique:
received:
15
01
2023
accepted:
19
09
2023
medline:
30
10
2023
pubmed:
17
10
2023
entrez:
17
10
2023
Statut:
ppublish
Résumé
Cleft palate has a multifactorial etiology. In palatal fusion, the contacting medial edge epithelium (MEE) forms the epithelial seam, which is subsequently removed with the reduction of p63. Failure in this process results in a cleft palate. We herein report the involvement of janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling in palatal fusion and that folic acid rescues the fusing defect by reactivating JAK2/STAT3. In closure of bilateral palatal shelves, STAT3 phosphorylation was activated at the fusing MEE and mesenchyme underlying the MEE. JAK2 inhibition by AG490 inhibited STAT3 phosphorylation and resulted in palatal fusion failure without removal of the epithelial seam, in which p63 and keratin 17 (K17) periderm markers were retained. Folic acid application restored STAT3 phosphorylation in AG490-treated palatal explants and rescued the fusion defect, in which the p63- and K17-positive epithelial seam were removed. The AG490-induced palatal defect was also rescued in p63 haploinsufficient explants. These findings suggest that JAK2/STAT3 signaling is involved in palatal fusion by suppressing p63 expression in MEE and that folate restores the fusion defect by reactivating JAK2/STAT3.
Identifiants
pubmed: 37846594
pii: 333518
doi: 10.1242/dmm.050085
pmc: PMC10602007
pii:
doi:
Substances chimiques
alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
0
STAT3 Transcription Factor
0
Janus Kinase 2
EC 2.7.10.2
Folic Acid
935E97BOY8
JAK2 protein, human
EC 2.7.10.2
STAT3 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
Références
J Clin Invest. 2014 Sep;124(9):3891-900
pubmed: 25133425
Birth Defects Res. 2020 Apr 15;112(7):555-568
pubmed: 32134217
Dev Biol. 2005 Feb 1;278(1):193-202
pubmed: 15649471
Cochrane Database Syst Rev. 2015 Dec 14;(12):CD007950
pubmed: 26662928
Curr Top Dev Biol. 2008;84:37-138
pubmed: 19186243
J Cell Biol. 1998 Oct 19;143(2):469-86
pubmed: 9786956
FASEB J. 2010 Nov;24(11):4167-74
pubmed: 20631328
BMC Genomics. 2013 Feb 20;14:113
pubmed: 23421592
Development. 2004 Jan;131(1):15-24
pubmed: 14645125
Nat Genet. 1999 May;22(1):69-73
pubmed: 10319864
Front Physiol. 2020 Oct 02;11:538835
pubmed: 33123019
Cell Signal. 2015 Jul;27(7):1356-68
pubmed: 25841994
Signal Transduct Target Ther. 2021 Nov 26;6(1):402
pubmed: 34824210
Annu Rev Neurosci. 2014;37:221-42
pubmed: 25032496
Int J Dev Biol. 2004 Jun;48(4):307-17
pubmed: 15300511
Am J Hum Genet. 2002 Jul;71(1):1-13
pubmed: 12037717
Stem Cells Dev. 2017 Jan 1;26(1):49-59
pubmed: 27676194
Oral Dis. 2022 Jul;28(5):1339-1350
pubmed: 35122708
Oncogene. 2000 Nov 16;19(48):5419-27
pubmed: 11114718
Dis Model Mech. 2022 Feb 1;15(2):
pubmed: 34897389
Development. 2012 Jan;139(2):231-43
pubmed: 22186724
Nat Genet. 2001 May;28(1):29-35
pubmed: 11326271
Sci Rep. 2016 Jun 22;6:28012
pubmed: 27329259
Teratology. 1968 Feb;1(1):33-49
pubmed: 5696816
J Cell Physiol. 2015 Jun;230(6):1212-25
pubmed: 25358290
Birth Defects Res. 2020 Nov;112(19):1699-1719
pubmed: 33118705
Dev Biol. 2008 Sep 1;321(1):273-82
pubmed: 18634775
J Clin Invest. 2004 Jun;113(12):1676-8
pubmed: 15199400
Genet Med. 2008 Sep;10(9):668-74
pubmed: 18978678
Dis Model Mech. 2019 Jun 27;12(6):
pubmed: 31171577
J Clin Invest. 2010 Jan;120(1):103-14
pubmed: 20038814
N Engl J Med. 1999 Mar 4;340(9):692-702
pubmed: 10053178
Sci Rep. 2018 Jul 25;8(1):11208
pubmed: 30046048
Am J Med Genet C Semin Med Genet. 2013 Nov;163C(4):333-56
pubmed: 24124024
Organogenesis. 2011 Oct-Dec;7(4):242-54
pubmed: 21964245
Nat Genet. 1995 Dec;11(4):409-14
pubmed: 7493021
Genes Dev. 2018 Sep 1;32(17-18):1175-1187
pubmed: 30135074
PLoS Genet. 2017 Jun 12;13(6):e1006828
pubmed: 28604778
Dev Biol. 2007 Jan 15;301(2):309-26
pubmed: 16942766
Development. 2013 Mar;140(6):1220-30
pubmed: 23406900
Am J Anat. 1977 Nov;150(3):477-99
pubmed: 930860
Oral Dis. 2010 Jan;16(1):11-9
pubmed: 20331806
Neoplasia. 2013 Jul;15(7):848-62
pubmed: 23814496
J Exp Clin Cancer Res. 2019 May 14;38(1):195
pubmed: 31088482
Nat Rev Cancer. 2009 Jun;9(6):400-14
pubmed: 19440234
Int J Cancer. 2016 Jun 1;138(11):2570-8
pubmed: 26559373
J Biol Chem. 2012 Feb 17;287(8):5819-32
pubmed: 22205702